Knockdown of long noncoding RNA MIAT attenuates hypoxia‐induced cardiomyocyte injury by regulating the miR‐488‐3p/Wnt/β‐catenin pathway

Abstract

Dysfunction of cardiomyocytes contributes to the development of acute myocardial infarction (AMI). Nonetheless, the regulatory mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in cardiomyocyte injury remains largely unclear. The cardiomyocyte injury was assessed via cell viability and apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and flow cytometry, respectively. The levels of MIAT, microRNA (miR)-488-3p, and Wnt5a were detected via quantitative real-time polymerase chain reaction and Western blot.After bioinformatical analysis, the binding between miR-488-3p and MIAT or Wnt5a was confirmed via dual-luciferase reporter, RNA immunoprecipitation, and RNA pulldown assays. Our results showed that MIAT expression was increased in AC16 cells after hypoxia treatment. Silencing of MIAT alleviated hypoxia-induced viability reduction, apoptosis increase, and Wnt/β-catenin pathway activation. MIAT directly targeted miR-488-3p. MiR-488-3p might repress hypoxia-induced cardiomyocyte injury, and its knockdown reversed the effect of MIAT depletion on cardiomyocyte injury. Wnt5a was validated as a target of miR-488-3p. Wnt5a expression restoration attenuated the influence of MIAT knockdown on hypoxia-triggered cardiomyocyte injury. Our findings demonstrated that downregulation of MIAT might mitigate hypoxia-induced cardiomyocyte injury partly through miR-488-3p mediated Wnt/β-catenin pathway.

MIAT LncRNA: A multifunctional key player in non-oncological pathological conditions

“…In a recent model of hypoxia-induced cardiomyocyte injury, another regulatory network governed by MIAT was unveiled. MIAT was found to suppress miR-488-3p, a miRNA known for its cardioprotective effects on cardiomyocyte injury, particularly through the downregulation of Wnt family member 5A (Wnt5A) [ 209 ]. The Wnt-β-catenin signaling pathway has been extensively discussed in the pathogenesis of MI [ 209 ].…”

“…MIAT was found to suppress miR-488-3p, a miRNA known for its cardioprotective effects on cardiomyocyte injury, particularly through the downregulation of Wnt family member 5A (Wnt5A) [ 209 ]. The Wnt-β-catenin signaling pathway has been extensively discussed in the pathogenesis of MI [ 209 ]. This suggests that the MIAT-miR-488-3p-Wnt5 axis may also play a role in the pathogenesis of MI, highlighting the importance of normalizing the expression of MIAT in MI patients.…”

“… Disease Expression Profile Validated Target Genes/Signaling pathway References Multiple Sclerosis Controversial SF1 CE1f3 QKI [ 49 , 155 , 166 , 168 , 169 , 176 ] Schizophrenia Controversial BMI1 Crybb1 [ 174 , 177 ] Ischemic stroke Upregulated miR-874-3p/IL-1β pathway [ 185 ] EGLN2 [ 186 ] REDD1 [ 187 ] Myocardial infarction Upregulated involvement in cardiomyocyte apoptosis [ 189 , 198 ] Activation of the PI3K/Akt signaling pathway [ 203 ] miR-24/furin/TGF-β1 [ 202 ] miR-203 [ 206 ] miR-10a-5p/EGR2 axis. [ 207 ] TSPO modulating mitochondrial membrane integrity in the infarct zone [ 208 ] Wnt-β-catenin signaling pathway [ 209 ] Coronary artery disease Upregulate...…”